The proposed research involves the synthesis of new folic acid antagonists for evaluation as potential antitumor agents. Of particular concern are tumors of the large bowel. The new compounds to be prepared will consist largely of quinazoline derivatives of naturally occurring folates. Both classical and nonclassical derivatives will be studied but particular emphasis will be given to polyglutamate forms. Most of the target compounds will be prepared on a micro scale and then forwarded to Dr. Joseph Bertino and his associates for in vitro evaluation against a variety of human tumor cell lines as well as for enzyme inhibition studies. Active compounds will then be scaled up for in vivo studies both alone and in combination with 5-fluorouracil.